Albendazole induces an anti-tumor effect and potentiates PD-L1 blockade immunotherapy

作者全名："Zhang, Weinan; He, Zhiqiang; Liang, Fucheng; Gong, Jie; Tan, Liuchang; Yang, Juan; Song, Siji; Xie, Luoyingzi; Lu, Yuangang"

作者地址："[Zhang, Weinan; Liang, Fucheng; Tan, Liuchang; Lu, Yuangang] Amy Med Univ, Army Med Ctr PLA, Dept Plast & Cosmet Surg, 10 Daping Changjiang Branch Rd, Chongqing, Peoples R China; [He, Zhiqiang] Chongqing Contemporary Plast Surg Hosp, Dept Plast & Cosmet Surg, Chongqing, Peoples R China; [Xie, Luoyingzi] Chongqing Gen Hosp, Inst Hepatopancreatobiliary Surg, 118 Xingguang Ave, Chongqing, Peoples R China; [Gong, Jie] Chongqing Med Univ, Sch Clin Med, Chongqing, Peoples R China; [Yang, Juan] 535th Hosp Peoples Liberat Army, Dept Digest, Huaihua, Hunan, Peoples R China; [Song, Siji] Army Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing, Peoples R China"

通信作者："Lu, YA (通讯作者)，Amy Med Univ, Army Med Ctr PLA, Dept Plast & Cosmet Surg, 10 Daping Changjiang Branch Rd, Chongqing, Peoples R China.; Xie, LYZ (通讯作者)，Chongqing Gen Hosp, Inst Hepatopancreatobiliary Surg, 118 Xingguang Ave, Chongqing, Peoples R China."

来源：JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001069066400002

JCR分区：Q3

影响因子：2.7

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Albendazole; Anti-PD-L1; Melanoma; Tumor

摘要："BackgroundPreviously, albendazole (ABZ) has been reported as an anti-parasitic drug rather than anti-tumor drug. Our study aim to investigate whether ABZ also has a potential anti-tumor effect by shaping the tumor immune microenvironment and interrogate whether ABZ could synergize with the PD-L1 blockade.MethodsC57BL/6 mice (C57) were intravenously injected with B16F10-luciferase (B16-luc) cells to establish a lung metastatic melanoma model and subcutaneously inoculated with B16-luc cells to establish a subcutaneous tumor model. The tumor volume and tumor metastasis loci of the mice were measured by a vernier caliper and in vivo imaging. RNA sequencing was performed to analyze the different genes and pathways of immune cells in the tumors. Flow cytometry and immunofluorescence were used to analyze the different subsets of tumor-infiltrating immune cells.ResultsThe results suggested that ABZ significantly inhibited lung melanoma metastasis with decreased fluorescence intensity and nodule score and mediated the regression of subcutaneous melanoma in mice with decreased tumor volume. Moreover, RNA sequencing results showed that ABZ regulated the gene expression levels and pathways of immune cells in the tumor microenvironment (TME). Meanwhile, flow cytometry and immunofluorescence showed that the number and percentage of CD8+ T cells, CD4+ T cells, and TH1 cells were enhanced in tumors after ABZ treatment. Furthermore, the combination of ABZ and anti-PD-L1 treatment significantly potentiated anti-tumor efficacy in both lung metastasis and subcutaneous melanoma models and mediated an increase in the percentage of CD8+ T cells, CD4+ T cells, and TH1 cells as compared to the control group.ConclusionABZ inhibits melanoma growth and metastasis. Moreover, ABZ synergized with PD-L1 blockade mediates tumor regression."

基金机构："This work was supported by research grants from the National Natural Science Foundation of China (Nos.81672694, 82272763). The authors would like to thank Prof. Wenyue Xu for providing laboratory support. [81672694, 82272763]; National Natural Science Foundation of China"

基金资助正文："This work was supported by research grants from the National Natural Science Foundation of China (Nos.81672694, 82272763). The authors would like to thank Prof. Wenyue Xu for providing laboratory support."